The primary objective of this proposal is to develop a highly sensitive method of analysis for amitriptylene, a widely used antidepressant drug. This drug produces very low blood levels following the administration of the usually recommended therapeutic doses. There is no satisfactory method available at present to determine these low levels. Our approach is based on applying new procedures developed in our laboratories during the past 3 years. In essence, the drug will be reacted with a specific compound and subsequently manipulated to yield fluorescence which can be measured. It is expected that the fully developed assay method will have a capability of determining 5 to 10 ng/ml of amitriptylene in blood and other tissues.